Mycophenolate mofetil and FK506: two novel immunosuppressants in murine corneal transplantation.
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Biomedical subjects
Publications and source records attributed to S Braunstein.
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Severe pancytopenia associated with moderate hepatosplenomegaly, increased serum lactic dehydrogenase (LDH) levels, and hypogammaglobulinemia were found in a young male patient. Bone marrow histology showed extensive fibrosis, hypoplasia of erythro- and granulocytopoiesis, and hyperplasia of megakaryocytopoiesis associated with histiocytic fat cell phagocytosis and infiltration of abnormal lymphocytes, compatible with lymphoid myelofibrosis. Striking chromosomal aberrations indicating karyotype evolution were also demonstrated by cytogenetic analyses (47, XY, +3 / 47, XY, +3, 1p+ / 46, XO, +3, 1p+, -Y). The clinical course was characterized by cyclic febrile episodes accompanied by excessive increase of serum LDH levels and leukocyte counts, and decrease of platelet counts, followed by spontaneous regression. Further diagnostic procedures, including two liver biopsies and computed tomography, did not detect any manifestation of lymphoma. Eventually, the patient developed rapidly progressive, lethal pulmonary aspergillosis. At autopsy, high grade B cell lymphoma of the liver was found. In this case, the lymphoid myelofibrosis seen on bone marrow biopsy may be considered as a manifestation of "discordant" bone marrow histology related to high grade lymphoma. With respect to the cyclic clinical course, a possible role of apoptotic mechanisms in the physiopathology of this disorder is reviewed.
In laser-controlled cartilage-ablation arthroplasties, the attention focuses more and more on the depth effects of the various lasers, especially as heat necroses of the cartilage and even in places of the bone were found in animal experiments. For the first time, two cases of holmium: YAG laser-induced aseptic bone necrosis of the femoral condyles after cartilage ablation are described.
Granulocyte/macrophage-colony-stimulating factor (GM-CSF), an immunomodulator of hematopoietic cells, has also been shown to stimulate human keratinocyte proliferation in vitro and speed healing of wounds in the skin of lepromatous leprosy patients. In this study we have examined the in vivo effects of recombinant human GM-CSF on epidermal keratinocyte proliferation and on expression of proteins marking regenerative epidermal growth. Skin biopsies from GM-CSF injected cutaneous sites were obtained between 1 and 6 d following administration of 7.5 or 15 micrograms of the growth factor. Activation of keratinocyte proliferation, quantified as the expression of the Ki67+ nuclear antigen, was noted 1 d following GM-CSF administration. A regenerative epidermal phenotype, demonstrated by immunohistochemical staining of cellular proteins involucrin, filaggrin, and keratin 16, was similarly noted as early as 1 d following GM-CSF injection. This phenotype persisted as late as 6 d post-injection. These results suggest that GM-CSF injection into human skin induces keratinocyte proliferation as well as regenerative differentiation of the epidermis. To date no other cytokine has been shown to be mitogenic for human keratinocytes both in vivo and in vitro or to alter keratinocyte differentiation along the "alternate" or regenerative pathway.
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A total of 90 regional lymph nodes (43 benign/47 metastatic) from 16 surgical resection specimens of patients with esophageal and gastric carcinoma were examined in vitro by endosonography. The validity of endosonographic criteria of lymph node dignity (size, echogenicity, internal echo pattern and margin structure) was assessed using computer-supported B-mode analysis and compared to histopathological results. Of 26 lymph nodes with a diameter of more than 10 mm, 19 were metastatic (72%). The subjective assessment of the internal echo pattern (homogeneity) and the node margins by an experienced observer allowed the diagnosis of metastatic lymph nodes, but there was a high proportion of false positives (52%). Lymph node echogenicity, assessed either subjectively or by computer analysis, did not permit the differentiation between benign and metastatic lymph nodes.
A 34-year-old Turkish woman presented with septic fever, sweats, arthralgia, and abdominal pain. Further examination revealed generalized lymphadenopathy, hepatosplenomegaly, pancytopenia, and multiple caseous granulomas. Microbiological diagnosis revealed Brucella melitensis type 3 as causative agent. This case report demonstrates that abdominal pain can be a symptom in brucellosis, and caseous granulomas may occur. In our mobile society Brucella infection should be considered as possible differential diagnosis in patients with fever, lymphadenopathy, hepatosplenomegaly, and pancytopenia, although human brucellosis is rare in Germany and other Western countries.
Between January 1986 and October 1991 255 patients with rectal tumors were treated by local excision. In 239 patients local excision was performed by transanal endoscopic microsurgery, 16 tumors were removed with the retractor developed by Parks. Operative mortality was 1% in 189 local removed adenomas, complications were observed in two patients (2.1%), local recurrences in seven patients (3.7%). 66 rectal carcinomas were treated by local excision (operative mortality 1%, complication rate 3%). In one of 28 local excised "low risk" T1-carcinomas a recurrence was observed. Five of eleven local treated patients with "high risk" tumors developed a recurrence. Endosonography was of utmost importance in preoperative staging of rectal tumors. Between June 1987 and October 1991 204 patients with rectal tumors (92 sessile adenomas, 30 T1-carcinomas and 82 advanced carcinomas) were examined preoperatively by endosonography. The diagnosis of an adenoma or a T1-carcinoma was made with a sensitivity of 0.9, although no differentiation was possible between adenomas and T1-carcinomas. Results of digital examination were comparable to endosonography, under condition that digital examination was complete. Insufficient information was obtained from the endosonographic detection of lymph-node metastatic spread.
From April 1989 to June 1991 63 patients with esophageal cancer were investigated by endosonography with the object of ascertaining the depth of intrathoracic tumor infiltration and lymphnode involvement. The sensitivity in diagnosing tumor infiltration amount to 0.74; the sensitivity for involvement of regional lymphnode was 0.84, specificity 0.44. In an in-vitro analysis endosonographic criteria for the assessment of regional lymphnodes are proved. Echogenic structure seems not to be a valuable criterium.
32 forceps biopsies were performed in 30 patients with obstructive jaundice during percutaneous transhepatic biliary drainage procedures. In one patient an adequate specimen could not be obtained. In 25 of the remaining 31 cases diagnosis was confirmed histologically (malignant tumours: n = 22, benign stricture: n = 3). In 6 patients false-negative results were obtained. Transluminal biopsy is an easily performed adjunct to percutaneous transhepatic diagnostic interventions with minimal additional discomfort for the patient. In many cases percutaneous needle biopsy can be avoided. Forceps biopsy enables nonoperative histological diagnosis of small carcinomas of the bile ducts.
59 patients with rectal cancer were treated by local excision. In 17 of these patients a radical resection was performed afterwards. In one of 21 local excised "low risk" T1-carcinomas a recurrence was observed. Five of 11 local treated patients with "high risk" tumours developed a recurrence. In the group of the radically treated patients two recurrences were seen. Regarding our results the local excision of "low risk" T1-carcinomas seems to be justified, if final histological workup reveals an adequate margin of healthy tissue.
Pre-operative staging was performed in 81 patients with rectal tumours by means of endorectal sonography. In 87% of cases (70 out of 81), the endosonographic findings corresponded with the histopathological appearance; the recognition of T0 and 1 tumours, which is important in deciding surgical procedures, was possible in 94% (51 out of 54). Differentiation between T0 and T1 tumours (i.e. between adenomas and carcinomas infiltrating the submucosa) was not possible. Five out of ten of T2 and 14 out of 16 T3 tumours were staged correctly. One T4 tumour was placed in too low a stage. A comparison of the echo structure of adenomas and carcinomas in 76 patients showed that 28 out of 43 adenomas (65%) have homogeneous echoes, while 24 out of 33 carcinomas (73%) showed inhomogeneous low intensity echoes.
Rectal carcinomas are amongst the most common malignant tumours. The aim of this work was to determine whether high resolution CT with thin sections (1 mm) can provide satisfactory delineation of perirectal tumour infiltration. Correct determination of local tumour spread was possible in four out of nine patients and distinction between those tumours confined to the rectal wall and those infiltrating the perirectal tissues was possible in four out of eight patients.
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Using the "transanal endoscopic microsurgery" technique, 140 patients were treated at the Department of Surgery in Cologne and Mainz. Of the patients with adenomas, 68.2% had typical symptoms preoperatively. The postoperative hospital attendance was 8.7 days, with an average resection size of 14.4 cm2. The postoperative complication rate was 5%, and there were no deaths related to the technique. In a prospective controlled trial, 2.2% of the patients with adenomas treated endoscopically in Mainz showed recidivation, requiring reoperation. The follow-up rate was 100%. In 30 cases, microscopic examination revealed carcinoma. Radical reoperation in 8 pT1 tumours showed neither remaining tumour nor lymph node metastases. Twelve patients with pT1 carcinoma treated by local surgery alone were recurrence-free with an average follow-up period of 12.3 months. So far, there have been no late results.
35 patients with rectal cancer were examined in a prospective trial by endorectal ultrasound. In 27 patients the sonographic diagnosis of tumour penetration was correct as compared with histologic findings, in 7 patients infiltration depth was overestimated, and in one case underestimated. In 21 resected specimens, examined postoperatively in a water tank with the same equipment, ultrasonic examination was correct in 17; in no case was the infiltration depth underestimated. The different technical approaches in local sonographic staging of rectal cancer are discussed.
Seventy-five patients with sessile adenomas or early carcinomas of the rectum or rectosigmoid were operated on with the new technique "transanal endoscopic microsurgery" Employing a newly developed complex endoscopic operating system, complete removal of sessile adenomas can be accomplished up to a distance of 25 cm from the anal verge, accurately and non-invasively. Complications occurred in three cases, with no resulting mortality. In the follow-up period we discovered only one adenomatous recurrence that required operative treatment. The superior accuracy of preparation, a short average stay in hospital, and low recurrence and complication rates are the advantages of this transanal endoscopic operative technique.